Neutrophil extracellular traps in COVID-19

In severe cases of coronavirus disease 2019 (COVID-19), viral pneumonia progresses to respiratory failure. Neutrophil extracellular traps (NETs) are extracellular webs of chromatin, microbicidal proteins, and oxidant enzymes that are released by neutrophils to contain infections. However, when not p...

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Vydáno v:	JCI insight Ročník 5; číslo 11
Hlavní autoři:	Zuo, Yu, Yalavarthi, Srilakshmi, Shi, Hui, Gockman, Kelsey, Zuo, Melanie, Madison, Jacqueline A., Blair, Christopher N., Weber, Andrew, Barnes, Betsy J., Egeblad, Mikala, Woods, Robert J., Kanthi, Yogendra, Knight, Jason S.
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	United States American Society for Clinical Investigation 04.06.2020
Témata:	Adult Aged Aged, 80 and over Biomarkers Blood platelets C-reactive protein C-Reactive Protein - metabolism Case-Control Studies Cell-Free Nucleic Acids - metabolism Chromatin Citrullination Citrulline Coronavirus Infections - blood Coronavirus Infections - metabolism Coronavirus Infections - therapy Coronaviruses COVID-19 Cytokines Dehydrogenases Deoxyribonucleic acid Disease DNA Enzymes Extracellular Traps - metabolism Female Fibrin Fibrinogen Degradation Products - metabolism Histone H3 Histones Histones - metabolism Hospitalization Humans In Vitro Techniques Infections Influenza L-Lactate dehydrogenase L-Lactate Dehydrogenase - metabolism Leukocytes (neutrophilic) Lymphocyte Count Male Mann-Whitney U test Mechanical ventilation Medical laboratories Microbicides Microvasculature Middle Aged Neutrophils Neutrophils - metabolism Oxidants Pandemics Patients Peroxidase Peroxidase - metabolism Platelet Count Pneumonia Pneumonia, Viral - blood Pneumonia, Viral - metabolism Pneumonia, Viral - therapy Respiration, Artificial Respiratory distress syndrome Respiratory failure Severe acute respiratory syndrome coronavirus 2 Severity of Illness Index Therapeutic targets Thrombosis Ventilators Infectious disease Inflammation Neutrophils
ISSN:	2379-3708, 2379-3708
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Popis
Shrnutí:	In severe cases of coronavirus disease 2019 (COVID-19), viral pneumonia progresses to respiratory failure. Neutrophil extracellular traps (NETs) are extracellular webs of chromatin, microbicidal proteins, and oxidant enzymes that are released by neutrophils to contain infections. However, when not properly regulated, NETs have the potential to propagate inflammation and microvascular thrombosis - including in the lungs of patients with acute respiratory distress syndrome. We now report that sera from patients with COVID-19 have elevated levels of cell-free DNA, myeloperoxidase-DNA (MPO-DNA), and citrullinated histone H3 (Cit-H3); the latter 2 are specific markers of NETs. Highlighting the potential clinical relevance of these findings, cell-free DNA strongly correlated with acute-phase reactants, including C-reactive protein, D-dimer, and lactate dehydrogenase, as well as absolute neutrophil count. MPO-DNA associated with both cell-free DNA and absolute neutrophil count, while Cit-H3 correlated with platelet levels. Importantly, both cell-free DNA and MPO-DNA were higher in hospitalized patients receiving mechanical ventilation as compared with hospitalized patients breathing room air. Finally, sera from individuals with COVID-19 triggered NET release from control neutrophils in vitro. Future studies should investigate the predictive power of circulating NETs in longitudinal cohorts and determine the extent to which NETs may be novel therapeutic targets in severe COVID-19.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	2379-3708 2379-3708
DOI:	10.1172/jci.insight.138999